A developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.

The way in which the information contained in genotypes is translated into complex phenotypic traits (i.e. embryonic expression patterns) depends on its decoding by a multilayered hierarchy of biomolecular systems (regulatory networks). Each layer of this hierarchy displays its own regulatory scheme...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autor principal:	Jayson Gutiérrez
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3786c0ff99fb4dda8f6b53f74d9b6da6
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3786c0ff99fb4dda8f6b53f74d9b6da6
record_format	dspace
spelling	oai:doaj.org-article:3786c0ff99fb4dda8f6b53f74d9b6da62021-11-25T06:20:32ZA developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.1932-620310.1371/journal.pone.0006823https://doaj.org/article/3786c0ff99fb4dda8f6b53f74d9b6da62009-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19738908/?tool=EBIhttps://doaj.org/toc/1932-6203The way in which the information contained in genotypes is translated into complex phenotypic traits (i.e. embryonic expression patterns) depends on its decoding by a multilayered hierarchy of biomolecular systems (regulatory networks). Each layer of this hierarchy displays its own regulatory schemes (i.e. operational rules such as +/- feedback) and associated control parameters, resulting in characteristic variational constraints. This process can be conceptualized as a mapping issue, and in the context of highly-dimensional genotype-phenotype mappings (GPMs) epistatic events have been shown to be ubiquitous, manifested in non-linear correspondences between changes in the genotype and their phenotypic effects. In this study I concentrate on epistatic phenomena pervading levels of biological organization above the genetic material, more specifically the realm of molecular networks. At this level, systems approaches to studying GPMs are specially suitable to shed light on the mechanistic basis of epistatic phenomena. To this aim, I constructed and analyzed ensembles of highly-modular (fully interconnected) networks with distinctive topologies, each displaying dynamic behaviors that were categorized as either arbitrary or functional according to early patterning processes in the Drosophila embryo. Spatio-temporal expression trajectories in virtual syncytial embryos were simulated via reaction-diffusion models. My in silico mutational experiments show that: 1) the average fitness decay tendency to successively accumulated mutations in ensembles of functional networks indicates the prevalence of positive epistasis, whereas in ensembles of arbitrary networks negative epistasis is the dominant tendency; and 2) the evaluation of epistatic coefficients of diverse interaction orders indicates that, both positive and negative epistasis are more prevalent in functional networks than in arbitrary ones. Overall, I conclude that the phenotypic and fitness effects of multiple perturbations are strongly conditioned by both the regulatory architecture (i.e. pattern of coupled feedback structures) and the dynamic nature of the spatio-temporal expression trajectories displayed by the simulated networks.Jayson GutiérrezPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 9, p e6823 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jayson Gutiérrez A developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.
description	The way in which the information contained in genotypes is translated into complex phenotypic traits (i.e. embryonic expression patterns) depends on its decoding by a multilayered hierarchy of biomolecular systems (regulatory networks). Each layer of this hierarchy displays its own regulatory schemes (i.e. operational rules such as +/- feedback) and associated control parameters, resulting in characteristic variational constraints. This process can be conceptualized as a mapping issue, and in the context of highly-dimensional genotype-phenotype mappings (GPMs) epistatic events have been shown to be ubiquitous, manifested in non-linear correspondences between changes in the genotype and their phenotypic effects. In this study I concentrate on epistatic phenomena pervading levels of biological organization above the genetic material, more specifically the realm of molecular networks. At this level, systems approaches to studying GPMs are specially suitable to shed light on the mechanistic basis of epistatic phenomena. To this aim, I constructed and analyzed ensembles of highly-modular (fully interconnected) networks with distinctive topologies, each displaying dynamic behaviors that were categorized as either arbitrary or functional according to early patterning processes in the Drosophila embryo. Spatio-temporal expression trajectories in virtual syncytial embryos were simulated via reaction-diffusion models. My in silico mutational experiments show that: 1) the average fitness decay tendency to successively accumulated mutations in ensembles of functional networks indicates the prevalence of positive epistasis, whereas in ensembles of arbitrary networks negative epistasis is the dominant tendency; and 2) the evaluation of epistatic coefficients of diverse interaction orders indicates that, both positive and negative epistasis are more prevalent in functional networks than in arbitrary ones. Overall, I conclude that the phenotypic and fitness effects of multiple perturbations are strongly conditioned by both the regulatory architecture (i.e. pattern of coupled feedback structures) and the dynamic nature of the spatio-temporal expression trajectories displayed by the simulated networks.
format	article
author	Jayson Gutiérrez
author_facet	Jayson Gutiérrez
author_sort	Jayson Gutiérrez
title	A developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.
title_short	A developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.
title_full	A developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.
title_fullStr	A developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.
title_full_unstemmed	A developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.
title_sort	developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/3786c0ff99fb4dda8f6b53f74d9b6da6
work_keys_str_mv	AT jaysongutierrez adevelopmentalsystemsperspectiveonepistasiscomputationalexplorationofmutationalinteractionsinmodeldevelopmentalregulatorynetworks AT jaysongutierrez developmentalsystemsperspectiveonepistasiscomputationalexplorationofmutationalinteractionsinmodeldevelopmentalregulatorynetworks
_version_	1718413796187308032

A developmental systems perspective on epistasis: computational exploration of mutational interactions in model developmental regulatory networks.

Ejemplares similares